Recent Advances in the Diagnosis, Pathogenesis, and Management of Myxoinflammatory Fibroblastic Sarcoma.

Myxoinflammatory fibroblastic sarcoma (MIFS) is an infiltrative, locally aggressive fibroblastic neoplasm of intermediate malignancy that typically arises in the distal extremities of middle-aged adults. It can histologically be confused with a number of benign and malignant conditions. Recently, high-grade examples of MIFS have been described. Immunohistochemistry plays a very limited role in the diagnosis of MIFS. Several genetic alterations have been identified in MIFS, including a t(1;10)(p22;q24) translocation with TGFBR3 and/or OGA rearrangements, BRAF rearrangement, and VGLL3 amplification. Although it appears that VGLL3 amplification is the most consistent alteration, the molecular pathogenesis of MIFS remains poorly understood. A wide resection is considered the standard treatment for MIFS. Radiotherapy may be a viable option in cases with inadequate surgical margins or cases where surgery is likely to cause significant functional impairment. The systemic treatment options for advanced or metastatic disease are very limited. This review provides an updated overview of the clinicoradiological features, pathogenesis, histopathology, and treatment of MIFS.

Fibrosarcoma primario de ovario. Reporte de una neoplasia inusual / Primary ovarian fibrosarcoma. Report of an unusual neoplasm

Introducción: El fibrosarcoma ovárico es un tumor maligno del estroma ovárico muy infrecuente, con pocos casos reportado en la literatura. Principales síntomas o hallazgos clínicos: Mujer de 56 años posmenopáusica, con sangrado vaginal escaso de varios días de evolución y dolor en fosa ilíaca derecha sin fiebre ni clínica digestiva. La exploración ginecológica era normal.Diagnósticos principales, intervenciones terapéuticas y resultados: La ecografía transvaginal mostró un endometrio homogéneo, un mioma de 2,4×1cm y una lesión sólido-quística heterogénea de tabiques gruesos de 6,4×6,8cm en el ovario izquierdo. El estudio histológico intraoperatorio se informó como: neoplasia sólida sospechosa de malignidad. Se le realizó histerectomía más doble anexectomía, omentectomía y linfadenectomía. Histológicamente la neoplasia estaba constituida por células fusiformes dispuestas en láminas y fascículos entrecruzados con apariencia difusa en espiga, con atipia nuclear moderada, áreas de necrosis y focos de hemorragia. Se identificaron 12 mitosis por 10 campos de gran aumento. Inmunohistoquímicamente las células fueron positivas para inhibina, actina 1A4, vimentina, calretinina, CD56 y CD99. El índice proliferativo con Ki-67 fue del 25%. El diagnosticó definitivo fue: fibrosarcoma primario de ovario. Un año después, la paciente se encontraba libre de enfermedad sin ninguna terapia adyuvante y continúa en seguimiento. Conclusión: El fibrosarcoma de ovario es una neoplasia maligna excepcional de mal pronóstico. En la actualidad, los tratamientos y factores pronósticos del fibrosarcoma ovárico siguen siendo discutibles. El presente caso destaca el importante papel del estudio intraoperatorio y la inmunohistoquímica para su correcto diagnóstico.(AU)

Introduction: Ovarian fibrosarcoma is an extremely rare malignant ovarian stromal tumor, with few cases reported in the literature. Main symptoms and/or clinical findings: A 56-year-old posmenopausal woman with scant vaginal bleeding of several days’ duration and pain in the right iliac fossa without fever or digestive symptoms. The gynecological examination was normal. Main diagnoses, therapeutic interventions and results: Transvaginal ultrasound showed a homogeneous endometrium, a 2.4×1cm myoma, and a heterogeneous solid-cystic lesion with thick septa measuring 6.4×6.8cm in the left ovary. An intraoperative histological study was performed, which was reported as: solid neoplasm suspicious of malignancy. Hysterectomy plus double adnexectomy, omentectomy, and lymphadenectomy were performed. Histologically, the neoplasm was made up of spindle cells arranged in sheets and intertwined fascicles with a diffuse spike-like appearance, with moderate nuclear atypia, areas of necrosis and hemorrhage foci; 12 mitoses were identified for every 10 high-power fields. Immunohistochemically the cells were positive for inhibin, actin 1A4, vimentin, calretinin, CD56 and CD99. The proliferative rate with Ki-67 was 25%. The definitive diagnosis was: primary ovarian fibrosarcoma. One year later, the patient is free of the disease without any adjuvant treatment and continues to be followed up. Conclusion: Ovarian fibrosarcoma is an exceptional malignancy with a poor prognosis. Currently, the treatments and prognostic factors for ovarian fibrosarcoma are still the subject of debate. This case highlights the important role of the intraoperative study and immunohistochemistry for its correct diagnosis.(AU)

Megakaryocytes Mediate Hyperglycemia-Induced Tumor Metastasis.

High blood glucose has long been established as a risk factor for tumor metastasis, yet the molecular mechanisms underlying this association have not been elucidated. Here we describe that hyperglycemia promotes tumor metastasis via increased platelet activity. Administration of glucose, but not fructose, reprogrammed the metabolism of megakaryocytes to indirectly prime platelets into a prometastatic phenotype with increased adherence to tumor cells. In megakaryocytes, a glucose metabolism-related gene array identified the mitochondrial molecular chaperone glucose-regulated protein 75 (GRP75) as a trigger for platelet activation and aggregation by stimulating the Ca2+-PKCα pathway. Genetic depletion of Glut1 in megakaryocytes blocked MYC-induced GRP75 expression. Pharmacologic blockade of platelet GRP75 compromised tumor-induced platelet activation and reduced metastasis. Moreover, in a pilot clinical study, drinking a 5% glucose solution elevated platelet GRP75 expression and activated platelets in healthy volunteers. Platelets from these volunteers promoted tumor metastasis in a platelet-adoptive transfer mouse model. Together, under hyperglycemic conditions, MYC-induced upregulation of GRP75 in megakaryocytes increases platelet activation via the Ca2+-PKCα pathway to promote cancer metastasis, providing a potential new therapeutic target for preventing metastasis. SIGNIFICANCE: This study provides mechanistic insights into a glucose-megakaryocyte-platelet axis that promotes metastasis and proposes an antimetastatic therapeutic approach by targeting the mitochondrial protein GRP75.

The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33.

In cancer, myeloid cells have tumor-supporting roles. We reported that the protein GPNMB (glycoprotein nonmetastatic B) was profoundly upregulated in macrophages interacting with tumor cells. Here, using mouse tumor models, we show that macrophage-derived soluble GPNMB increases tumor growth and metastasis in Gpnmb-mutant mice (DBA/2J). GPNMB triggers in the cancer cells the formation of self-renewing spheroids, which are characterized by the expression of cancer stem cell markers, prolonged cell survival and increased tumor-forming ability. Through the CD44 receptor, GPNMB mechanistically activates tumor cells to express the cytokine IL-33 and its receptor IL-1R1L. We also determined that recombinant IL-33 binding to IL-1R1L is sufficient to induce tumor spheroid formation with features of cancer stem cells. Overall, our results reveal a new paracrine axis, GPNMB and IL-33, which is activated during the cross talk of macrophages with tumor cells and eventually promotes cancer cell survival, the expansion of cancer stem cells and the acquisition of a metastatic phenotype.

Clinical and molecular characterization of primary sclerosing epithelioid fibrosarcoma of bone and review of the literature.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare sarcoma subtype characterized by monomorphic epithelioid cells embedded in a densely sclerotic collagenous matrix. The overwhelming majority of tumors arise in soft tissues; however, rare cases have been documented to occur primarily in bone. The hallmarks of soft tissue SEF include MUC4 immunoreactivity and the presence of an EWSR1-CREB3L1 fusion. Rare cases with alternative fusions have also been reported such as EWSR1-CREB3L2 and FUS-CREB3L2 transcripts. The molecular alterations of skeletal SEF have not been well-defined, with only rare cases analyzed to date. In this study we investigated the clinicopathologic and molecular features of seven patients presenting with primary osseous SEF. There were 3 males and 4 females, with a mean age at diagnosis of 38 years. All cases had microscopic features within the histologic spectrum of SEF and showed strong and diffuse MUC4 positivity, while lacking SATB2 expression. However, due to its unusual presentation within bone, four cases were initially misinterpreted as either osteosarcoma, Ewing sarcoma or chondroblastoma. Half of the patients with follow-up data developed metastasis. The cases were tested by targeted RNA sequencing, MSK-IMPACT, and/or fluorescence in situ hybridization, showing EWSR1-CREB3L1 in six cases and EWSR1-CREB3L2 in one case. The fusion transcripts were composed of EWSR1 exon 11 to either exon 6 of CREB3L1 or CREB3L2. In summary, due to their rarity in the bone, skeletal SEF are often misdiagnosed, resulting in inadequate treatment modalities. Similar to their soft tissue counterpart, bone SEF follow an aggressive clinical behavior and show similar EWSR1-CREB3L1/CREB3L2 fusions.

PTX3 Modulates Neovascularization and Immune Inflammatory Infiltrate in a Murine Model of Fibrosarcoma.

Fibrosarcoma is an aggressive subtype of soft tissue sarcoma categorized in infantile/congenital-type and adult-type. Fibrosarcoma cells and its surrounding immune inflammatory infiltrates overexpress or induce the expression of fibroblast growth factor-2 (FGF-2) that have a crucial role in tumor progression and angiogenesis. The inflammation-associated long pentraxin 3 (PTX3) was found to reduce FGF-2-mediated angiogenesis, but its role on fibrosarcoma immune inflammatory infiltrate is still unknown. In this study, we have evaluated the PTX3 activity on immune infiltrating mast cells, macrophages and T-lymphocytes by immunohistochemistry on murine MC-TGS17-51 fibrosarcoma cells and on transgenic TgN(Tie2-hPTX3) mouse. In these fibrosarcoma models we found a reduced neovascularization and a significant decrease of inflammatory infiltrate. Indeed, we show that PTX3 reduces the level of complement 3 (C3) deposition reducing fibrosarcoma progression. In conclusion, we hypothesize that targeting fibrosarcoma microenvironment by FGF/FGFR inhibitors may improve treatment outcome.

Low-Grade Sinonasal Sarcoma With Neural and Myogenic Features: A Recently Discovered Entity With Unique Features and Diagnostic Challenge.

Low-grade sinonasal sarcoma with neural and myogenic features is an entity recently described in the literature. Little is known about its etiopathogenesis, natural history, or optimal treatment. In fact, it has relatively unique findings: it has a distinctive cytogenetic signature, and it expresses both smooth muscle actin and S100 protein. However, its diagnosis is challenging on biopsies showing negative staining for these 2 markers. The differential diagnoses include fibrosarcoma, malignant peripheral nerve sheath tumors, and other benign and malignant lesions. A complete resection, with or without radiotherapy, is required because this lesion appears to be locally aggressive. However, the clinical outcome seems to be good. Low-grade sinonasal sarcoma with neural and myogenic features merits classification as an independent tumor in the next World Health Organization classification of head and neck tumors. Reports of additional cases are required to support its unique classification.

A Comparison of Dose Metrics to Predict Local Tumor Control for Photofrin-mediated Photodynamic Therapy.

This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [1 O2 ]rx , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm-2 ) and in-air fluence rates (50-150 mW cm-2 ) at Photofrin dosages of 5 and 15 mg kg-1 and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [1 O2 ]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [1 O2 ]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [1 O2 ]rx ≥ 1.1 mm or PDT dose ≥1200 µm J cm-2 but cannot be predicted with fluence alone. LCR increases with increasing [1 O2 ]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [1 O2 ]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.

Prognosis of Fibrosarcoma in Patients With and Without a History of Radiation for Nasopharyngeal Carcinoma.

PURPOSE: To determine whether radiation-induced fibrosarcoma (RIF) in patients with a history of radiotherapy for nasopharyngeal carcinoma (NPC) was associated with an inferior prognosis compared to sporadic fibrosarcoma of the head and neck. METHODS: Forty-two patients with RIF who previously received radiotherapy for NPC and 124 patients with sporadic fibrosarcoma of the head and neck were identified between January 1965 and December 2013 at our institution. Information on clinicopathologic characteristics and treatment was abstracted from medical records. The primary end point was disease-specific survival (DSS). RESULTS: The median latency from NPC diagnosis to RIF diagnosis was 9.9 years (range 3.1-36.8 years). RIF was diagnosed at an older age than sporadic fibrosarcoma. Treatment modality was significantly different between the two groups, with only 64.3 % of the RIF group receiving surgery ± adjuvant treatment versus 91.1 % in the sporadic fibrosarcoma group (P < 0.001). Patients with RIF had poorer 5-year DSS compared to the sporadic fibrosarcoma group (36.2 vs. 50.4 %; P = 0.026). Multivariate analysis of the combined group indicated that patient group (P = 0.032), tumor, node, metastasis classification system stage (P = 0.019), histologic grade (P = 0.046) and treatment modality (P < 0.001) were independent variables affecting DSS. CONCLUSIONS: Compared to patients with sporadic fibrosarcoma, NPC survivors who develop RIF are older at diagnosis of fibrosarcoma and have an inferior prognosis.

Sarcoma miofibroblástico posradioterapia / Radiation-induced myofibroblastic sarcoma

Paciente de 51 años, varón, fumador y alcohólico moderado, con síntomas de disfonía intermitente que debuta con una adenopatía cervical metastásica de carcinoma epidermoide, sin hallazgos del tumor primario. Es intervenido quirúrgicamente siéndole realizada una disección cervical unilateral y posteriormente es tratado con quimiorradioterapia concomitante. A los 4 años del final del tratamiento oncológico, sin recidiva local ni aparición del tumor primario, el paciente debuta con disnea de presentación subaguda. Tras la exploración física y pruebas diagnósticas, se constata una nueva tumoración en laringe que resulta ser un "sarcoma miofibroblástico de bajo grado". Según los criterios de Cahan, este tumor, de estirpe histológica poco frecuente en laringe, hace pensar que probablemente podría ser inducido por la radiación. Se discuten los criterios de causalidad entre radiación y oncogenesis y se resumen las características de los tumores radioinducidos.

We report a clinical case about a male patient, smoker and alcoholic, that debuts with a neck metastasis of an epidermoid carcinoma of unknown origin. He was submitted to a cervical dissection and treated with adjuvant combined chemo and radio therapy. Four years after finishing the oncologic treatment without tumor recurrence or appearence of the primary tumor, he begins with sub acute dyspnea. After physical examination and imaging, a new larynx tumor was found, "low grade myofibroblastic sarcoma". Under Cahan criteria, this tumoral kind, rare in larynx, was probably induced by the local radiotherapy. We discuss briefly the causality between radiation and oncogenesis and the characteristics of the radio induced tumors.

Secondary Neoplasms in Children with Hodgkin's Lymphoma Receiving C-MOPP and Radiotherapy: Presentation of Four Cases.

Patients who survive Hodgkin lymphoma (HL) are at increased risk of secondary neoplasms (SNs). A wide variety of SNs have been reported, including leukemias, non-Hodgkin's lymphomas, and solid tumors, specifically breast and thyroid cancers. Herein we report subsequent neoplasms in four patients with HL receiving chemoradiotherapy. It is interesting that three SNs, fibrosarcoma, thyroid carcinoma, and retrobulbar meningioma, were observed in the radiation area in one of our patients. A hypopharyngeal epithelioid malignant peripheral nerve sheath tumor as an unusual secondary malignant neoplasm developed in another patient, while a benign thyroid nodule and invasive ductal breast carcinoma were observed at different times in the female patient. Follicular adenoma of the thyroid gland developed in one of our patients.

Fibrosarcoma arising from gouty tophi: report of a unique case and review of literature.

Fibrosarcoma is a malignant mesenchymal tumor. To the author's best knowledge, no previous case of fibrosarcoma arising from gouty tophi has been reported. Here we reported the first case of fibrosarcoma arising from gouty tophi. A case of 58-year-old man was presented with a mass with ulcer and infection in the second joint of left middle finger for 2 months, with long standing gouty tophi. The tumor was biopsied and the biopsy showed complete excision of the tumor. With the pathological and immunohistochemical features considered, the diagnosis of fibrosarcoma associated with gouty tophi was made. The clinical findings, pathological characteristics and treatment were described.

Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling.

PURPOSE: To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single-dose or clinically relevant, fractioned-dose γ-ray radiation. METHODS AND MATERIALS: C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2-Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days after irradiation, and all tumors were characterized histologically. RESULTS: A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed after fractionated irradiation (16.4%) in comparison with single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation tumor observed (n=201), with carcinomas occurring less frequently (n=9). The proportion of mice developing tumors increased significantly with total dose for both single-dose and fractionated schedules, and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice after single-dose irradiation; however, significant differences in tumor susceptibilities after fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common after fractionated irradiation, whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common after single-dose irradiation. CONCLUSIONS: This study investigated the tumorigenic effect of acute large doses in comparison with fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiation therapy. Differences in tumor histotype after single-dose or fractionated radiation exposures provide novel in vivo evidence for differences in tumor susceptibility among stromal cell populations.

Inflammation-Related Tumor Progression in Murine Fibrosarcoma Exhibited Over-expression of Sex-determining Region Y-box 2 (Sox2) Compared to Parental Regressor Cells.

BACKGROUND/AIM: Tumor progression is one of the most serious issues to overcome cancer disease. As a model of inflammation-induced tumor progression, we used the regressive murine fibrosarcoma cell clone QR-32 and the progressive malignant clone QRsP-11, that was derived from QR-32. Heat shock protein beta-1 (Hspb1) is a molecular chaperone. Hspb1 plays roles in not only cell protection but also chemo-resistance, tumorigenicity and protection from apoptosis. In a recent study, we showed that Hspb1 was up-regulated in QRsP-11 compared to QR-32. MATERIALS AND METHODS: We compared the expression levels of Hspb1, Hsf1 and Sox2 in QR-32 and QRsP-11 cells by means of western blotting. RESULTS: Hsf1, a transcription factor for Hspb1 was not increased in QRsP-11. Sex determining region Y-box 2 (Sox2) is a transcription factor, reported to interact with Hspb1. Sox2 was up-regulated in QRsP-11 compared to QR-32. CONCLUSION: These results suggest that Sox2-Hspb1 signaling is a possible pathway responsible to tumor progression of QRsP-11.

Subcutaneous fluid port-associated soft tissue sarcoma in a cat.

A 20-year-old male castrated domestic longhair cat was evaluated for assessment of its chronic kidney disease (CKD) and a non-healing ulcerated mass at the site of a previously placed and subsequently removed GIF tube. The cat had been diagnosed with CKD 10 years prior and two GIF tubes had been placed over a 5-year period, the second of which was associated with secondary infection. Biopsy of the non-healing ulcerated mass was consistent with grade 2 soft tissue sarcoma. At necropsy there was a discrete, serpentine, subcutaneous mass measuring approximately 8 mm in diameter that extended approximately 20 cm along the dorsum to the caudal thorax, following the path of the GIF tube, from the main intrascapular, ulcerated mass where the fluid port injection site was located. This is the first report of a fibrosarcoma arising at the site of a subcutaneous fluid port in a cat. Although the cat's owners were pleased with the 4 years of quality of life provided by this device, this complication should be considered when a decision to place ports for long-term management of disease is made.

Computed tomography characteristics of fibrosarcoma -- a histological subtype of feline injection-site sarcoma.

Feline injection-site sarcoma (FISS) may be a consequence of subcutaneous injection. In the present study, the medical records and the computed tomography (CT) features of 22 cats with a FISS, histopathological subtype fibrosarcoma, were used. The majority of the fibrosarcomas (45%) were located in the interscapular region. All fibrosarcomas, except one with mild enhancement, showed strong contrast uptake, characterised as ring (42%), heterogeneous (36%), homogeneous (9%), heterogeneous/ring (6.5%) or mixed heterogeneous/homogeneous enhancement (6.5%). The longest axis of the mass was in a cranio-caudal (68%) or dorso-ventral (32%) direction. The median volume calculated on CT was 7.57 cm(3). Common features were a marked local invasiveness of the musculature and heterogeneity of the tissue in the periphery of the neoplasia. When the fibrosarcoma was interscapular, performing an additional post-contrast scan with the forelimbs positioned caudally along the body, in addition to the standard protocol with the forelimbs extended cranially, allowed better evaluation of the actual relationship between the tumour and the surrounding tissues. The mean number of muscles involved with the tumour was 2.09 with extended and 1.95 with flexed forelimbs. When a lower number of structures was considered infiltrated through the double positioning, a less invasive surgical approach to underlying muscles and scapula was performed.

High-grade myxofibrosarcoma presenting at the spermatic cord after radiotherapy for prostate cancer.

A 72-year-old man with a history of prostate cancer presented 7 years postradiotherapy with a painless, egg-sized, rapidly growing nodule on the left groin at the radiation site. He underwent left high orchiectomy under a diagnosis of groin lymph node metastasis of prostate cancer. The tumour had penetrated deep into the internal inguinal ring and was resected as proximally as possible to the internal ring with a positive surgical margin. Macroscopically, the left testis was intact in the resected specimen. Immunohistochemical staining revealed that the tumour consisted of myxofibrosarcoma (MFS) with spindle cells; and was positive for vimentin, cytokeratin (AE1/AE3), MIB-1 and CD68, and negative for α-SMA, S-100, CD34 and myogenin. Thus, the tumour was diagnosed as high-grade MFS of the spermatic cord. Postoperative CT revealed a right renal tumour and adrenal tumour. Right radial nephrectomy was performed and the patient was doing well at 10-month follow-up.

Myxofibrosarcoma of the sinus piriformis: case report and literature review.

Myxofibrosarcoma is a common sarcoma in the extremities of older people, but is rare in the head and neck region. Here, we report the case of a 42-year-old male patient in whom myxofibrosarcoma generated from the sinus piriformis. Histopathologically, the tumor was characterized by spindle cellular proliferation with moderate cellular density in fibromyxoid stroma. Immunohistochemically, the tumor cells showed positive reactivity for vimentin, Ki-67, smooth muscle actin, and CD34, but negative staining for S-100. Based on these results, the tumor was diagnosed as a low-grade myxofibrosarcoma. Resection of the tumor was performed via a transcervical approach. The patient's postoperative clinical course was uneventful and no local recurrence or distant metastasis has been found so far. The pathology, clinical characteristics, and treatment of myxofibrosarcoma are also reviewed.

Neonatal soft tissue sarcomas.

Soft tissue tumors in very young children pose diagnostic and therapeutic challenges. Vascular tumors are the most prevalent soft tissue neoplasms in the neonatal period. They are generally benign tumors, but may exhibit aggressive behaviour and cause life-threatening complications. Fibroblastic tumors of intermediate prognosis, more prevalent in very young children (especially infantile fibrosarcoma), are locally aggressive. Since metastases are unusual in this group of tumors, complete surgical resection is generally curative. However, these tumors often present a therapeutic challenge because of the location which makes complete surgical resection difficult. Among the malignant soft tissue tumors, rhabdomyosarcoma is most frequent. It is an aggressive high-grade tumor, with local invasiveness and a propensity to metastasize. These tumors respond to chemotherapy and radiotherapy. Neonates with rhabdomyosarcoma seem to have a worse prognosis than in older age groups. This may be a result of inappropriate dosing of chemotherapeutic agents and decreased use of radiation therapy among other factors.